ANDROGEN-DEPENDENT SYNTHESIS OF α2u GLOBULIN IN THE RAT: ROLE OF THE PITUITARY GLAND

Roy, Arun K.

doi:10.1677/joe.0.0560295

Cited by 89 publications

(24 citation statements)

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“…Thus, glucagon concentration is increased in starvation (42), and this results in a decrease in concentration of nuclear T3 receptor sites as well as in the activity of ME (43). Other examples of multihormonal regulation of cellular responses include the regulation of a2U globulin messenger RNA in rats by testosterone and glucocorticoids, in addition to thyroid hormones (44,45) and the synergistic regulation of growth hormone production by glucocorticoid and thyroid hormones in cultured growth hormone-producing pituitary tumor cell lines (46,47). The possibility exists that products from the tumor itself may have influenced cellular metabolism in the present studies.…”

Section: Discussionmentioning

confidence: 99%

Response of hepatic mitochondrial alpha-glycerophosphate dehydrogenase and malic enzyme to constant infusions of L-triiodothyronine in rats bearing the Walker 256 carcinoma. Evidence for divergent postreceptor regulation of the thyroid hormone response.

Tibaldi¹,

Sahnoun²,

Surks³

1984

J. Clin. Invest.

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Aatract. To characterize the hepatic response to L-triiodothyronine (T3) in an experimental nonthyroidal disease, we determined the activity of hepatic mitochondrial a-glycerophosphate dehydrogenase (a-GPD) and cytosol malic enzyme (ME) as a function of the saturation of the nuclear T3 receptor during constant T3 infusions in rats bearing the Walker 256 carcinoma. Groups of control and tumor-bearing rats were infused by minipumps (Alza Corp., Palo Alto, CA) with vehicle, 1.2 or 4.5 Ag T3/100 body wt per day for 3 d. The range for serum T3 was 47.2±4.1 to 165±17.3 ng/dl for the control rats and 13.2±1.3 to 135±14.3 ng/dl for the tumor-bearing rats. Nuclear T3 receptor concentration was between 0.41±0.06 and 0.47±0.02 ng/mg DNA in control rats and was decreased in tumor-bearing rats to between 0.23±0.03 and 0.26±0.03 ng/mg DNA. Nuclear T3 receptor concentrations were not influenced by the T3 infusions. Specifically bound nuclear T3, determined by radioimmunoassay of extracts of isolated nuclei, was decreased nearly 50% in the tumor-bearing rats. However, the calculated percentage saturation of the T3 nuclear receptor remained similar in control and tumor-bearing rats at each level of T3 infusion. Dose-response curves for a-GPD and ME were curvilinear and showed an This work was presented in part at the 59th annual meeting of the American Thyroid Association, New Orleans, Louisiana, October 5-8, 1983. Address reprint requests to Dr. Surks, Montefiore Medical Center. Receivedfor publication 20 December 1983 and in revisedform 18 April 1984.exponential increase in enzyme activity with progressive receptor saturation. In tumor-bearing rats, the activity curves or calculated appearance rate curves for a-GPD were shifted significantly upward and to the left, indicating greater sensitivity to T3, and those of ME were shifted downward and to the right, indicating decreased responsiveness to T3. Our findings suggest that cellular factors result in postreceptor amplification of the a-GPD response and diminution of the ME response to T3 in tumor-bearing rats. Augmentation of the a-GPD response may be a prototype for other hormonal responses that enable the tumor-bearing rat to maintain an apparent euthyroid state in association with decreased serum T3.

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Section: Discussionmentioning

confidence: 99%

Response of hepatic mitochondrial alpha-glycerophosphate dehydrogenase and malic enzyme to constant infusions of L-triiodothyronine in rats bearing the Walker 256 carcinoma. Evidence for divergent postreceptor regulation of the thyroid hormone response.

Tibaldi¹,

Sahnoun²,

Surks³

1984

J. Clin. Invest.

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“…Antiserum to pure azU globulin was prepared by injecting emulsions of pure aZu globulin with Freund's complete adjuvant into rabbits, as described earlier [15]. Both by the criteria of immunodiffusion and immunoelectrophoresis, the antiserum was found to be monospecific against a2,, globulin.…”

Section: Purfication Of Az Globulin and Preparation Of Rabbit Antismentioning

confidence: 99%

Early Events in the Steroidal Regulation of α_2u Globulin in Rat Liver

Roy

1977

European Journal of Biochemistry

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1. A double-antibody radioimmunoassay for azU globulin has been developed. With the help of this highly sensitive radioimmunoassay the early effects of both androgen and estrogen treatments on the hepatic synthesis of azU globulin in the rat have been investigated.2. Results show that the earlier observation of the long lag period in the androgenic induction of azU globulin is more apparent than real.3. Single injections of either Sa-dihydrotestosterone (Sa-dihydro-17~-hydroxy-4-androsten-3-one) or its physiological antagonist estradiol-17P (1,3,5(1O)-estratriene-3,17fl-diol) to castrated female rats resulted in the induction of azU globulin reaching maximum hepatic level of the protein between 6 -9 h after the hormone administration. Administration of cycloheximide 15 min prior to hormone treatment blocked both androgenic and estrogenic induction of mu globulin.4. Daily pretreatments with 5a-dihydrotestosterone increased the sensitivity of subsequent androgenic response to azU globulin synthesis. On the other hand, daily pretreatments with estradiol17p decreased and ultimately abolished the estrogenic induction of azu globulin.5. The possible mechanism of both androgenic and estrogenic induction of azU globulin in rat liver mediated through a sex-hormone-binding protein with dual affinity for both dihydrotestosterone and estradiol has been suggested. a2,, Globulin is the principal urinary protein in the mature male rat and the hepatic origin of the protein has been well documented [1-31. m u globulin is absent in the female and immature male rat; it appears initially in the male at the time of puberty (6-7 weeks of age) and reaches peak levels at about 12 weeks of age [4-61. Androgen treatment of spayed female rats has been found to result, after an initial lag period of 3-4 days, in the induction of both azu globulin and its corresponding messenger RNA (mRNA) in the liver [4,7]. On the other hand, estrogen treatment to mature male rats results in the suppression and ultimately complete inhibition of azU synthesis [4]. A cytosol androgen-binding protein in rat liver with additional affinity for estradiol17p has been identified [8]. There appears to be a strong correlation between the presence of this androgen-binding protein and the androgen-dependent synthesis of azu globulin in rat liver. Prepubescent, senescent and pseudohermaphrodite male rats which do not contain this hepatic androgen-binding protein This paper is dedicated to the memory of Professor Arthur H. Smith.Trivial Names. Estradiol-17p or estradiol, 1,3,5(10)-estratriene-3,17/?-diol; 5a-dihydrotestosterone or dihydrotestosterone, 5a-dihydro-17P-hydroxy-4-androsten-3-one. also do not respond to androgen treatment with azU induction. Androgen treatment to castrated female rats results in the rise of the level of the cytosol androgen-binding protein and on the other hand, estrogen treatment leads to gradual decrease and ultimate loss of the androgen-binding protein of rat liver [8,91. The body of experimental evidence on steroidal regulation of gen...

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“…This protein is absent or marginally detectable in the liver and urine of female and immature male rats (4); its hepatic synthesis increases in the male rat at puberty, reaching peak levels at about 9-12 weeks of age and decreasing to nearly undetectable levels in senescence (5). The hepatic synthesis of a2u-globulin is under multihormonal control; androgen, glucocorticoid, thyroid hormone, insulin, and growth hormone are required for the excretion of normal levels of a2u-globulin by adult male rats (4,6,7). Estrogen administered to mature male rats dramatically inhibits a2u-globulin synthesis (8), whereas androgen administered to ovariectomized female rats induces its synthesis (3).…”

mentioning

confidence: 99%

Developmental and hormonal regulation of alpha 2u-globulin gene transcription.

Kulkarni¹,

Gubits²,

Feigelson³

1985

Proc. Natl. Acad. Sci. U.S.A.

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Hepatic a2.-globulin protein and RNA levels are under developmental and complex multihormonal control. The present studies directly evaluate the degree to which this regulation is transcriptional. a2.-Globulin transcription was determined by measuring nuclear runoff RNA in vitro, and tissue a2.-globulin mRNA levels were measured by dot blot hybridization. These studies reveal that (i) a2u-Globulin, a protein of molecular weight 18,700 (1), is synthesized in the liver, secreted into the blood, and excreted in the urine of male rats (2). a2u-Globulin represents 1-2% of total protein synthesis in the liver (3). This protein is absent or marginally detectable in the liver and urine of female and immature male rats (4); its hepatic synthesis increases in the male rat at puberty, reaching peak levels at about 9-12 weeks of age and decreasing to nearly undetectable levels in senescence (5). The hepatic synthesis of a2u-globulin is under multihormonal control; androgen, glucocorticoid, thyroid hormone, insulin, and growth hormone are required for the excretion of normal levels of a2u-globulin by adult male rats (4, 6, 7). Estrogen administered to mature male rats dramatically inhibits a2u-globulin synthesis (8), whereas androgen administered to ovariectomized female rats induces its synthesis (3). We have recently reported that a2u-globulin is also synthesized in the submaxillary salivary gland (9) and in the extra-orbital lachrymal gland (10).a2u-Globulin is encoded by a multigene family of approximately 20 highly homologous members (11, 12). At least four of these a2u-globulin genes are expressed in the liver (1, 12), and different subsets of a2u-globulin genes are expressed in the salivary and lachrymal glands (9, 10). Thus, the a2u-globulin system provides an interesting opportunity to study processes underlying hormonal, developmental, and tissue-specific gene expression. Toward this end, we have cloned and sequenced one a2u-globulin gene and a number of hepatic (1, 12), salivary gland (9), and lachrymal gland (unpublished data) cDNAs.In the case of developmental (13, 14) and endocrine (3,8,(14)(15)(16)(17)(18)(19)(20) EXPERIMENTAL PROCEDURES Animals, Hormone Supplement, and Recombinant DNA. Intact and hypophysectomized Sprague-Dawley rats (Charles River Breeding Laboratories) were used in all experiments. Evaluation of complete hypophysectomy and duration and dosage of hormonal supplementations were as described earlier (14). For chronic estrogen administration male rats, 280-320 g, were used and 1713-estradiol (Sigma), 2 mg/kg of body weight, was injected intraperitoneally as described (8). The clones, 207-4, containing the entire a2u-globulin gene, and pSGII, containing a2u-globulin cDNA, have been described in detail (9, 12).Transcription in Isolated Nuclei. Nuclei were isolated from rat liver essentially as described by Mulvihill and Palmiter (24). The procedure for in vitro nuclear transcription, isolation of RNA, and hybridization is similar to that described by McKnight and Palmiter (25). Nuclei...

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ANDROGEN-DEPENDENT SYNTHESIS OF α2u GLOBULIN IN THE RAT: ROLE OF THE PITUITARY GLAND

Cited by 89 publications

References 11 publications

Response of hepatic mitochondrial alpha-glycerophosphate dehydrogenase and malic enzyme to constant infusions of L-triiodothyronine in rats bearing the Walker 256 carcinoma. Evidence for divergent postreceptor regulation of the thyroid hormone response.

Response of hepatic mitochondrial alpha-glycerophosphate dehydrogenase and malic enzyme to constant infusions of L-triiodothyronine in rats bearing the Walker 256 carcinoma. Evidence for divergent postreceptor regulation of the thyroid hormone response.

Early Events in the Steroidal Regulation of α_2u Globulin in Rat Liver

Developmental and hormonal regulation of alpha 2u-globulin gene transcription.

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ANDROGEN-DEPENDENT SYNTHESIS OF α2u GLOBULIN IN THE RAT: ROLE OF THE PITUITARY GLAND

Cited by 89 publications

References 11 publications

Response of hepatic mitochondrial alpha-glycerophosphate dehydrogenase and malic enzyme to constant infusions of L-triiodothyronine in rats bearing the Walker 256 carcinoma. Evidence for divergent postreceptor regulation of the thyroid hormone response.

Response of hepatic mitochondrial alpha-glycerophosphate dehydrogenase and malic enzyme to constant infusions of L-triiodothyronine in rats bearing the Walker 256 carcinoma. Evidence for divergent postreceptor regulation of the thyroid hormone response.

Early Events in the Steroidal Regulation of α2u Globulin in Rat Liver

Developmental and hormonal regulation of alpha 2u-globulin gene transcription.

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Early Events in the Steroidal Regulation of α_2u Globulin in Rat Liver